JAK3 is a member of the Janus family of protein kinases. Although the other members of this family are expressed by essentially all tissues, JAK3 expression is limited to hematopoetic cells. This is consistent with its essential role in signaling through the receptors for IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21 by non-covalent association of JAK3 with the gamma chain common to these multichain receptors. XSCID patient populations have been identified with severely reduced levels of JAK3 protein or with genetic defects to the common gamma chain, suggesting that immunosuppression should result from blocking signaling through the JAK3 pathway. Animals studies have suggested that JAK3 not only plays a critical role in B- and T-lymphocyte maturation, but that JAK3 is constitutively required to maintain T-cell function. Modulation of immune activity through this novel mechanism can prove useful in the treatment of T cell proliferative disorders such as transplant rejection and autoimmune diseases.
WO 2004/099205 discloses an JAK3 inhibitor represented by the following formula:
(For the Symbols in the Formula, Refer to the Gazette.)
WO 2004/099204 discloses an JAK3 inhibitor represented by the following formula:
(For the Symbols in the Formula, Refer to the Gazette.)
WO 99/65908, WO 99/65909, WO 01/42246, and WO 02/00661 disclose an JAK3 inhibitor represented by the following formula:
(For the Symbols in the Formula, Refer to the Gazette.)